The congenital hepatic porphyrias are a group of disorders which are characterized by alterations in the porphyrin-heme biosynthetic pathway. Although the human porphyrias constitute several distinct disorders, the increased activity of delta-aminolevulinic acid synthetase, normally the rate-limiting enzyme in heme pathway, appears to be partially responsible for the overproduction of the porphyrin and porphyrin precursors. This enzyme is induced by a variety of drugs which may result in acute attacks. A number of compounds have been tested for porphyrin-inducing capacity using several animal model systems, but most often a drug will stimulate delta-aminolevulinic acid synthetase in one system and not in another. Because of the clinical implications concerning the effects of drugs in the hereditary hepatic porphyrias, a reliable experimental mammalian model is needed. My objective is to use a primary culture of adult rat liver cells which remain viable for several weeks in vitro. The porphyrogenic drug, allylisopropylacetamide (AIA), will be used to elucidate the mechanism of drug-exacerbated porphyria by studying the effect of this barbiturate analog on the induction of delta-aminolevulinic acid synthetase. Included in these studies will be the effect of AIA on the levels of cytochrome P-450 and heme oxygenase. Since heme regulates delta-aminolevulinic acid synthetase by feedback inhibition, its utilization by cytochrome P-450, the major hemoprotein of the liver, and degradation by heme oxygenase are important in the overall control of porphyrin and heme synthesis.